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Supramolecular assembly and properties of dendrimeric peptide mimics
|Zofia Lipkowska 1, Marta K. Sowińska 1, Paulina Zielińska 1, Magdalena Zimnicka 1, Jolanta Solecka 2,3, Aleksandra M. Rajnisz , Tanja Lind 4, Marité Cárdenas 4
1. Instytut Chemii Organicznej Polskiej Akademii Nauk (ICHOPAN), Kasprzaka 44/52, Warszawa 01-224, Poland
Intermolecular interactions at various levels are driving forces of biological, chemical and physical processes, Therefore, their knowledge is essential in medicinal chemistry, particularly in the designing of a new therapeutic substances.
During last 20 years, dendrimeric compounds gained a lot of recognition as prospective carriers of poorly soluble substances in therapy of numerous diseases and as diagnostic tools. Although structural variability and globular structure of dendrimeric compounds were recognized early, de novo design of new original compounds for technology and medicine is still not very popular. Particularly in the case of dendrimeric peptides, intrinsically non-active amino acid residues after assembling on dendrimeric tree achieve new biological dimensions
Here we present rationale behind synthetic design of various types of biologically active peptide dendrimers and studies on their conformation and molecular assembly in various media. In particular, interactions with biologically relevant monovalent (Na+ and K+) and divalent (Mg2+ and Ca2+) cations, and impact of high concentrations (i.e. physiological conditions) on biological activity will be presented. Molecular assembly of the selected dendrimers with model zwitterionic and anionic phospholipids, studied in the gas phase by electrospray ionization mass spectrometry along with application of quartz crystal microbalance technique, revealed details of dendrimer-membrane interactions on molecular level.
Studies on influence of high salt conditions on antimicrobial potency and interactions with phospholipids might be important for knowledge of bactericidal mechanism and establishing similarities between mechanistic behavior of the natural linear antimicrobial peptides and the title branched peptidomimetic molecules.
Financial support from the National Center for Research and Development, grant NR13-0153-10/2010 and in part grant N204 239436 from the Ministry of Sciences and Higher Education, are acknowledged.
Presentation: Oral at VIII Multidyscyplinarna Konferencja Nauki o Leku, by Zofia Lipkowska
See On-line Journal of VIII Multidyscyplinarna Konferencja Nauki o Leku
Submitted: 2012-03-15 12:44 Revised: 2012-03-15 12:44